Predictors of recurrence following laparoscopic minor hepatectomy for hepatocellular carcinoma in the UK.

AIMS: Minor hepatectomy, which is increasingly carried out laparoscopically (LLR), is a cornerstone of curative treatment for hepatocellular carcinoma (HCC). The majority of relevant publications however originate from regions with endemic viral hepatitis. Although the incidence of HCC in the UK is increasing, little is known about outcomes following LLR. METHODS: Consecutive patients undergoing minor (involving ≤2 segments) LLR or open resection (OLR) at our institute between 2014 and 2021 were compared. Selection from a plethora of factors potentially impacting on overall (OS) and disease free survival (DFS) was optimised with Lasso regression. To enable analysis of patients having repeat resection, multivariate frailty modelling was utilised to calculate hazard ratios (HR). RESULTS: The analysis of 111 liver resections included 55 LLR and 56 OLR. LLR was associated with a shorter hospital stay (5 ± 2 vs. 7 ± 2 days; p < 0.001) and a lower comprehensive complication index (4.43 vs. 9.96; p = 0.006). Mean OS (52.3 ± 2.3 vs. 49.9 ± 3.0 months) and DFS (33.9 ± 3.4 vs. 36.5 ± 3.6 months; p = 0.59) were comparable between LLR and OLR, respectively (median not reached). Presence of mixed cholangiocarcinoma/HCC, satellite lesions and AFP level predicted OS and DFS. In addition tumour size was predictive of DFS. CONCLUSIONS: In the studied population minor LLR was associated with shorter hospital stay and fewer complications while offering non-inferior long-term outcomes. A number of predictors for disease free survival have been elucidated that may aid in identifying patients with a high risk of disease recurrence and need for further treatment.

Short- and long-term mortality after liver transplantation in patients with and without hepatocellular carcinoma in the UK.

BACKGROUND: The increasing demand for liver transplantation has led to considerable changes in characteristics of donors and recipients. This study evaluated the short- and long-term mortality of recipients with and without hepatocellular carcinoma (HCC) in the UK between 1997 and 2016. METHODS: First-time elective adult liver transplant recipients in the UK were identified and four successive eras of transplantation were compared. Hazard ratios (HRs) comparing the impact of era on short-term (first 90 days) and longer-term (from 90 days to 5 years) mortality were estimated, with adjustment for recipient and donor characteristics. RESULTS: Some 1879 recipients with and 7661 without HCC were included. There was an increase in use of organs donated after circulatory death (DCD), from 0 per cent in era 1 to 35·2 per cent in era 4 for recipients with HCC, and from 0·2 to 24·1 per cent for non-HCC recipients. The 3-year mortality rate decreased from 28·3 per cent in era 1 to 16·9 per cent in era 4 (adjusted HR 0·47, 95 per cent c.i. 0·35 to 0·63) for recipients with HCC, and from 20·4 to 9·3 per cent (adjusted HR 0·44, 0·36 to 0·53) for those without HCC. Comparing era 4 with era 1, improvements were more marked in short-term than in long-term mortality, both for recipients with HCC (0-90 days: adjusted HR 0·20, 0·10 to 0·39; 90 days to 5 years: adjusted HR 0·52, 0·35 to 0·75; P = 0·043) and for non-HCC recipients (0-90 days: adjusted HR 0·32, 0·24 to 0·42; 90 days to 5 years: adjusted HR 0·52, 0·40 to 0·67; P = 0·024). CONCLUSION: In the past 20 years, the mortality rate after liver transplantation has more than halved, despite increasing use of DCD donors. Improvements in overall survival can be explained by decreases in short-term and longer-term mortality.

ANTECEDENTES: La creciente demanda de trasplante hepático ha determinado cambios considerables en las características de los donantes y receptores. En este estudio, se evaluó la mortalidad a corto y a largo plazo de los receptores de trasplante hepático por carcinoma hepatocelular (hepatocelular carcinoma, HCC) y no-HCC en el Reino Unido entre 1997 y 2016. MÉTODOS: Se identificaron los receptores adultos de un primer trasplante hepático electivo en el Reino Unido y se compararon cuatro eras sucesivas de trasplante. Se estimaron los cocientes de riesgos instantáneos ajustados (adjusted hazard ratio, aHR) que comparaban el impacto de la era en la mortalidad a corto plazo (primeros 90 días) y a largo plazo (de 90 días a 5 años) ajustando por las características del receptor y del donante. RESULTADOS: Se incluyeron 1.879 receptores HCC y 7.661 receptores no-HCC. Hubo un aumento en el uso de donantes después de parada cardíaca (donors following circulatory death, DCD) del 0% en la era 1 al 35,2% en la era 4 para los receptores HCC y del 0,2% al 24,1% para los receptores no-HCC. La mortalidad a los 3 años disminuyó de 28,3% en la era 1 a 16,9% en la era 4 (aHR 0,47, i.c. del 95% 0,35-0,63) para receptores HCC y de 20,4% a 9,3% (aHR 0,44, 0,36-0,53) para receptores no-HCC. Comparando la era 1 y la era 4, las mejoras en la mortalidad a corto plazo fueron más marcadas que en la mortalidad a largo plazo, tanto para receptores HCC (aHR 0-90 días 0,20, 0,10-0,39; 90 días-5 años 0,52, 0,35-0,75; P =舁0,04) como para receptores no-HCC (aHR 0-90 días 0,32, 0,24-0,42; 90 días-5 años 0,52, 0,40-0,67; P =舁0,02). CONCLUSIÓN: En los últimos 20 años, la mortalidad después del trasplante de hígado se ha reducido a más de la mitad, a pesar del uso cada vez mayor de donantes DCD. Las mejoras en la supervivencia global pueden explicarse por la disminución de la mortalidad a corto y largo plazo.

Liver transplantation outcomes after transarterial chemotherapy for hepatocellular carcinoma.

BACKGROUND: Transarterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) awaiting liver transplantation is widespread, although evidence that it improves outcomes is lacking and there exist concerns about morbidity. The impact of TACE on outcomes after transplantation was evaluated in this study. METHODS: Patients with HCC who had liver transplantation in the UK were identified, and stratified according to whether they received TACE between 2006 and 2016. Cox regression methods were used to estimate hazard ratios (HRs) for death and graft failure after transplantation adjusted for donor and recipient characteristics. RESULTS: In total, 385 of 968 patients (39·8 per cent) received TACE. Five-year patient survival after transplantation was similar in those who had or had not received TACE: 75·2 (95 per cent c.i. 68·8 to 80·5) and 75·0 (70·5 to 78·8) per cent respectively. After adjustment for donor and recipient characteristics, there were no differences in mortality (HR 0·96, 95 per cent c.i. 0·67 to 1·38; P = 0·821) or graft failure (HR 1·01, 0·73 to 1·40; P = 0·964). The number of TACE treatments (2 or more versus 1: HR 0·97, 0·61 to 1·55; P = 0·903) or the time of death after transplantation (within or after 90 days; P = 0·291) did not alter the outcome. The incidence of hepatic artery thrombosis was low in those who had or had not received TACE (1·3 and 2·4 per cent respectively; P = 0·235). CONCLUSION: TACE delivered to patients with HCC before liver transplant did not affect complications, patient death or graft failure after transplantation.

ANTECEDENTES: La quimioembolización transarterial (transarterial chemoembolization, TACE) en pacientes con carcinoma hepatocelular (hepatocellular carcinoma, HCC) se utiliza como puente al trasplante hepático, aunque falta evidencia de que mejore los resultados y la morbilidad relacionada es motivo de preocupación. En este estudio se evaluó el impacto de la TACE en los resultados tras el trasplante para analizar las complicaciones. MÉTODOS: Se identificaron los receptores de trasplante hepático por HCC en el Reino Unido y se estratificaron según si habían recibido TACE entre 2006 y 2016. Se utilizó el método de regresión de Cox para estimar los cocientes de riesgos instantáneos (hazard ratio, HR) para la mortalidad post-trasplante y el fallo del injerto ajustados por las características del donante y del receptor. RESULTADOS: En total, 385 (39,8%) de 968 pacientes recibieron TACE, observándose similar supervivencia del paciente a los 5 años después del trasplante: 75,2% (i.c. del 95%: 68,8% a 80,5%) con TACE y 75,0% (70,5% a 78,8 %) sin TACE. Después de ajustar según las características del donante y del receptor, no hubo diferencias en la mortalidad (HR: 0,96, 0,67 a 1,38; P = 0,82) o en el fallo del injerto (HR: 1,01, 0,73 a 1,40; P = 0,96). El número de tratamientos con TACE (≥ 2 tratamientos TACE HR: 0,97, 0,61 a 1,55; P = 0,90) o el período de tiempo después del trasplante (mortalidad del paciente antes o después de 90 días; P = 0,29) no alteró el resultado. La incidencia de trombosis de la arteria hepática fue baja en aquellos que recibieron TACE o no (1,3% y 2,5%, respectivamente; P = 0,23). El fallo del injerto debido a eventos oclusivos fue similar en el grupo de pacientes que recibieron TACE (8,0% o 11/137) o que no la recibieron (6,7% o 5/75) TACE (P = 0,74). CONCLUSIÓN: La administración de TACE en pacientes con HCC antes del trasplante hepático no influyó en las complicaciones post-trasplante, la mortalidad del paciente o el fallo del injerto.

Does Preoperative Beta-blocker Use Influence Intraoperative Hemodynamic Profile and Post-operative Course of Liver Transplantation?

OBJECTIVE: We compared the intraoperative hemodynamic profiles and outcomes of liver transplant (LT) patients receiving preoperative beta-blockers for portal hypertension with those of patients not receiving beta-blockers. METHODS: Beat-to-beat hemodynamic data were recorded with the use of a lithium dilution cardiac output monitor, including heart rate (HR), cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), SVR index, mean arterial pressure, stroke volume (SV), and SV index. Perioperative data included age, sex, etiology of cirrhosis, Model of End-Stage Liver Disease score, warm and cold ischemia times, and intraoperative blood and blood products replacement. Postoperative data included Acute Physiology and Chronic Health Evaluation II score, Intensive Care National Audit and Research Centre (ICNARC) score, length of intensive care unit stay, renal replacement treatment, and mortality. RESULTS: After exclusion, 215 patients not receiving and 93 patients receiving beta-blockers for portal hypertension were included. There was no significant difference between groups in demographic data. HR, CO, and CI were significantly lower in the beta-blocker group (P = .0001). Regarding outcomes, the ICNARC score was significantly higher in the beta-blocker group (P < .05). CONCLUSIONS: Preoperative administration of beta-blockers attenuates the hyperdynamic circulation in LT patients; this is clearly seen through a reduction in intraoperative CO, CI, and HR. This decreased hyperdynamic state was not shown to relate to outcomes in any of the variables except for a higher ICNARC score reported in the group treated with beta-blockers.

Patient perception of skin-cancer prevention and risk after liver transplantation.

INTRODUCTION: Sun exposure is a major risk factor for the development of skin cancer. This is particularly relevant in immunosuppressed liver-transplant recipients (LTRs). Preventative strategies may help minimize the skin-cancer risk in this patient group. METHODS: We assessed 670 patients in our post-transplant clinic, using questionnaires. Patient data were collected, and we assessed whether patients had received education (such as formal talks or information from transplant coordinators or from hepatologists) on skin, sun exposure and skin cancer. In a subset of 280 of the LTRs who responded, we recorded their recall of sun-protection advice and assessed the level of patient adherence to such advice. RESULTS: The response rate was 57.5% (349/607), with a mean responder age of 51.1 years (range 19-84) and an average post-transplant time of 7.1 years (range 0-27). In the recall assessment, 37.2% reported that they were given advice about their skin, while 18.1% were seen by a dermatologist, and education on sun exposure and the risks of skin cancer was given to 65.6% and 47.9%, respectively. Over three-quarters (78%; 185/280) of the patients used mechanical sun protection (i.e. hats/clothing), while 66% reported using sunscreen; 31.8% of these used a sunscreen of the recommended sun protection factor (SPF) of > 30. Twelve patients had developed squamous cell carcinoma after a mean of 10.9 years (1-23) post-transplant; half of these had used either no sunscreen or one with an SPF of < 15. CONCLUSIONS: Despite the fact that LTRs are given information on sun-exposure and SC before and after transplantation, recall of such advice and use of sun-protection methods was only moderate, indicating that regular reinforcement of SC education is needed.

Systematic review: the role of liver transplantation in the management of hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality worldwide. Liver transplantation offers a potential cure for this otherwise devastating disease. The selection of the most appropriate candidates is paramount in an era of graft shortage. AIM: To review systematically the role of liver transplantation in the management of HCC in current clinical practice. METHODS: An electronic literature search using PUBMED (1980-2010) was performed. Search terms included HCC, hepatoma, liver cancer, and liver transplantation. RESULTS: Liver transplantation is a highly successful treatment for HCC, in patients within Milan criteria (MC), defined as a solitary tumour ≤50 mm in diameter or ≤3 tumours ≤30 mm in diameter in the absence of extra-hepatic or vascular spread. Other eligibility criteria for liver transplantation are also used in clinical practice, such as the University of California, San Francisco criteria, with outcomes comparable to MC. Loco-regional therapies have a role in the bridging treatment of HCC by minimising wait-list drop-out secondary to tumour progression. Beyond MC, encouraging results have been demonstrated for patients with down-staged tumours. Post-liver transplantation, there is no evidence to support a specific immunosuppressive regimen. In the context of an insufficient cadaveric donor pool to meet demand, the role of adult living donation may be increasingly important. CONCLUSIONS: Liver transplantation offers a curative therapy for selected patients with HCC. The optimisation of eligibility criteria is paramount to ensure that maximum benefit is accrued. Although wait-list therapies have been incorporated into clinical practice, additional high quality data are required to support this strategy.

Emerging strategies in the treatment of advanced hepatocellular carcinoma: the role of targeted therapies.

Hepatocellular cancer (HCC) is the fifth most common cause of cancer worldwide and its incidence is increasing as a result of the dissemination of hepatitis B and C virus infection. Surgical resection and liver transplantation are considered the only cures for HCC, but benefit approximately 10-15% of patients. In addition, radiofrequency ablation may is potentially curative for patients' with small HCC. Some patients with unresectable disease confined to the liver may benefit from embolisation or chemoembolisation. In the presence of disease not amenable to loco-regional therapy, median survival is only a few months. Current systemic therapy with cytotoxic chemotherapy induces relatively few responses and has no clear survival benefit. Current interest is focussed on the potential role of targeted therapies based on the key aspects of molecular pathogenesis of HCC, most notably sorafenib, an oral multikinase inhibitor. Recent developments discussed in this article demonstrate the potential benefits of this drug which seems destined to become first-line therapy for advanced HCC.